Oral premalignant lesions (OPLs) offer a unique human model for the study of biobehavioral risk factors because these lesions are associated with a well-defined risk for subsequent cancer development and are easy to monitor. Accumulating data suggest that human papillomavirus (HPV) infection of the oral mucosa may contribute to the development or malignant transformation of oral precancers. However, because not all OPLs progress to cancer, other factors (e.g., immune dysregutation) are believed to contribute to carcinogenesis. Psychological studies have demonstrated that psychosocial and behavioral factors have immunologic correlates, which could have implications for immune surveillance and control of viral infections such as HPV. The objectives of the proposed project are to: 1) examine the relationship between host immune factors and disease outcomes (e.g., progression, regression) within a model of OPLs; and 2) investigate potential psychosocial (e.g., distress) and behavioral (e.g., smoking) moderators of immune response. Guided by a biobehavioral model of cancer risk and progression, the proposed project employs a prospective, longitudinal design to evaluate the potential interrelations among psychosocial and behavioral risk factors, cell-mediated immunity, and progression of premaiignant oral lesions. Seventy-three patients with OPLs presenting at a large, urbandental clinic or referred to Fox Chase Cancer Center will be recruited at diagnosis. Participants will be asked to complete a questionnaire assessing psychosocial and behavioral factors and to provide a blood sample for relevant immune measures, including quantitative (e.g., enumeration of lymphocyte subsets) and functional (e.g., T-cell proliferative response to HPV) assays. Detection of HPV DNA in biopsy tissue will be assessed using polymerase chain reaction (PCR) techniques. Follow-up assessments of psychosocial, behavioral, and immune factors will be conducted 6-months postbaseline, and disease status (e.g., regression, new primary lesion) will be assessed. In addition, 73 healthy individuals will be accrued to provide "normal" baseline comparison levels of psychosocial, behavioral, and relevant immunologic measures. Altogether, the data collected will help elucidate the biobehavioral mechanisms underlying increased cancer risk within a model of OPLs, which may have important implications for developing psychosocial and behavioral interventions designed to reduce cancer risk.